Is OGDH p.Pro89= (c.267G>A) pathogenic?

OGDH p.Pro89= (c.267G>A) is classified Likely benign in OGDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). Very rare (popmax 0.00223%, eas); Associated with oxoglutaricaciduria.

What condition is associated with OGDH p.Pro89= (c.267G>A)?

OGDH p.Pro89= (c.267G>A) is associated with oxoglutaricaciduria (ClinVar).

How common is OGDH p.Pro89= (c.267G>A) in the general population?

OGDH p.Pro89= (c.267G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Oxoglutaric aciduria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

OGDH p.Pro89=

c.267G>A · rs745663966 · VCV2200895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

oxoglutaricaciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.1	GERP -3.9
Overall
CADD	3.512	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00118% 19/1,613,940 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
East Asiangrpmax	0.00223%	44,880
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00127%	78,667

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: OGDH
Protein: p.Pro89=
Coding: c.267G>A
MANE Select: NM_002541
dbSNP: rs745663966
Type: single nucleotide variant
Location: chr7:44645371 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.73 · 3 PDB

Full OGDH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

oxoglutaricaciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Oxoglutaric aciduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

OGDH p.Arg204Trp Uncertain significance ★★ ⚠ same condition
OGDH p.Asn709Ser Uncertain significance ★★ ⚠ same condition
OGDH p.Asp811Glu Uncertain significance ★★ ⚠ same condition
OGDH p.Lys532Arg Uncertain significance ★★ ⚠ same condition
OGDH p.Ser1023Leu Uncertain significance ★★ ⚠ same condition
OGDH p.Thr15Met Uncertain significance ★★ ⚠ same condition
OGDH p.Thr610Met Uncertain significance ★★ ⚠ same condition
OGDH p.Thr615Ile Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ogdh-p-pro89 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown